This proposal examines how pre-synaptic input plays a role in the development and growth of post-synaptic cells and organs, and determines how opiate-induced alterations of neuronal development and/or function can produce post-synaptic developmental abnormalities. Development of pre- and post-synaptic function of neurotransmitter systems will be followed in brain, heart and adrenal medulla by a combination of biochemical, functional and morphological procedures. These will determine normal and drug-altered development of synaptic contacts, synaptic uptake mechanisms, synaptic vesicles and post-synaptic response systems (receptors, ornithine decarboxylase, secretory systems). Correlations will be evaluated between alterations at the pre-synaptic level and those at the post-synaptic level involving neurotransmission and growth of the innervated tissue including morphological correlates of biochemical alterations. Perinatal addiction models are chosen which mimic prenatal maternal methadone addiction, addiction during postnatal development and neonatal withdrawal. Systems to be studied include dopaminergic mechanisms in corpus striatum, noradrenergic mechanisms in cerebral cortex, heart and adrenal medulla, serotonergic mechanisms in midbrain and brainstem and recepors for endogenous opiates in various brain regions. These different models will thus elucidate the role of opiate-induced alterations of neuronal input in development of central and peripheral post-synaptic systems and will identify specific biochemical and morphological alterations in pre-synaptic and post-synaptic development associated with perinatal addiction and/or withdrawal.